CCR1 mediates Müller cell activation and photoreceptor cell death in macular and retinal degeneration
Mononuclear cells are involved in the pathogenesis of retinal diseases, including age-related macular degeneration (AMD). Here, we examined the mechanisms that underlie macrophage-driven retinal cell death. Monocytes were extracted from patients with AMD and differentiated into macrophages (hMdɸs),...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/81208 |
| _version_ | 1827778726079758336 |
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| author | Sarah Elbaz-Hayoun Batya Rinsky Shira Hagbi-Levi Michelle Grunin Itay Chowers |
| author_facet | Sarah Elbaz-Hayoun Batya Rinsky Shira Hagbi-Levi Michelle Grunin Itay Chowers |
| author_sort | Sarah Elbaz-Hayoun |
| collection | DOAJ |
| description | Mononuclear cells are involved in the pathogenesis of retinal diseases, including age-related macular degeneration (AMD). Here, we examined the mechanisms that underlie macrophage-driven retinal cell death. Monocytes were extracted from patients with AMD and differentiated into macrophages (hMdɸs), which were characterized based on proteomics, gene expression, and ex vivo and in vivo properties. Using bioinformatics, we identified the signaling pathway involved in macrophage-driven retinal cell death, and we assessed the therapeutic potential of targeting this pathway. We found that M2a hMdɸs were associated with retinal cell death in retinal explants and following adoptive transfer in a photic injury model. Moreover, M2a hMdɸs express several CCRI (C-C chemokine receptor type 1) ligands. Importantly, CCR1 was upregulated in Müller cells in models of retinal injury and aging, and CCR1 expression was correlated with retinal damage. Lastly, inhibiting CCR1 reduced photic-induced retinal damage, photoreceptor cell apoptosis, and retinal inflammation. These data suggest that hMdɸs, CCR1, and Müller cells work together to drive retinal and macular degeneration, suggesting that CCR1 may serve as a target for treating these sight-threatening conditions. |
| first_indexed | 2024-03-11T14:38:52Z |
| format | Article |
| id | doaj.art-4eec9bad72744e968b8e36639e51e910 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-11T14:38:52Z |
| publishDate | 2023-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-4eec9bad72744e968b8e36639e51e9102023-10-30T15:48:15ZengeLife Sciences Publications LtdeLife2050-084X2023-10-011210.7554/eLife.81208CCR1 mediates Müller cell activation and photoreceptor cell death in macular and retinal degenerationSarah Elbaz-Hayoun0https://orcid.org/0009-0006-8605-5775Batya Rinsky1Shira Hagbi-Levi2https://orcid.org/0000-0002-2891-0079Michelle Grunin3https://orcid.org/0000-0002-3155-2858Itay Chowers4https://orcid.org/0000-0003-1897-4973Department of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, IsraelMononuclear cells are involved in the pathogenesis of retinal diseases, including age-related macular degeneration (AMD). Here, we examined the mechanisms that underlie macrophage-driven retinal cell death. Monocytes were extracted from patients with AMD and differentiated into macrophages (hMdɸs), which were characterized based on proteomics, gene expression, and ex vivo and in vivo properties. Using bioinformatics, we identified the signaling pathway involved in macrophage-driven retinal cell death, and we assessed the therapeutic potential of targeting this pathway. We found that M2a hMdɸs were associated with retinal cell death in retinal explants and following adoptive transfer in a photic injury model. Moreover, M2a hMdɸs express several CCRI (C-C chemokine receptor type 1) ligands. Importantly, CCR1 was upregulated in Müller cells in models of retinal injury and aging, and CCR1 expression was correlated with retinal damage. Lastly, inhibiting CCR1 reduced photic-induced retinal damage, photoreceptor cell apoptosis, and retinal inflammation. These data suggest that hMdɸs, CCR1, and Müller cells work together to drive retinal and macular degeneration, suggesting that CCR1 may serve as a target for treating these sight-threatening conditions.https://elifesciences.org/articles/81208CCR1macrophageMüller cellatrophic AMDretinagliosis |
| spellingShingle | Sarah Elbaz-Hayoun Batya Rinsky Shira Hagbi-Levi Michelle Grunin Itay Chowers CCR1 mediates Müller cell activation and photoreceptor cell death in macular and retinal degeneration eLife CCR1 macrophage Müller cell atrophic AMD retina gliosis |
| title | CCR1 mediates Müller cell activation and photoreceptor cell death in macular and retinal degeneration |
| title_full | CCR1 mediates Müller cell activation and photoreceptor cell death in macular and retinal degeneration |
| title_fullStr | CCR1 mediates Müller cell activation and photoreceptor cell death in macular and retinal degeneration |
| title_full_unstemmed | CCR1 mediates Müller cell activation and photoreceptor cell death in macular and retinal degeneration |
| title_short | CCR1 mediates Müller cell activation and photoreceptor cell death in macular and retinal degeneration |
| title_sort | ccr1 mediates muller cell activation and photoreceptor cell death in macular and retinal degeneration |
| topic | CCR1 macrophage Müller cell atrophic AMD retina gliosis |
| url | https://elifesciences.org/articles/81208 |
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